The goal of the proposed research is to use the newly synthesized High Specific Activity 123I-2'-Iodococaine (Specific Activity = 2.5 x 105 Ci/mmol) suitable for in-vivo cocaine receptor population imaging in the brain, and 125I-2'-Iodococaine (Specific Activity = 2200 Ci/mmol) suitable for in-vitro cocaine receptor site characterization. For the evaluation of these compounds as potential probes for the in-vivo and in-vitro characterization of the cocaine receptor sites we plan to perform the following experiments: 1) To study the in-vitro binding and inhibition of binding of 125I-2'- Iodococaine (Specific Activity 2200 Ci/mmol), by various drugs at the cocaine receptor sites in baboon brain caudate putamen and heart cell membranes to determine Bmax, Kd and IC50 and perform competition experiments with such drugs as nomifensine, (-)-cocaine, GBR 12909, desipramine and others. 2) To study the in-vivo binding and inhibition of binding of 123I-2'-Iodococaine (Specific Activity 2.5 x 105 Ci/mmol) in the baboon brain using dynamic imaging with a gamma camera. 3) To confirm by autopsy and autoradiography the presence, the sites and identity of the radioactive metabolites in the brain and heart of the baboon. 4) To correlate the in-vivo and in-vitro data to try to map the brain and heart for cocaine receptor population. Such a "cocaine receptor probe", radiolabeled with a short-lived pure gamma emitter with an ideal gamma energy i.e. 123I, could potentially be used for Single Photon Emission tomography (SPECT) imaging as a diagnostic tool in Nuclear Medicine to study the difference, if any, in cocaine receptor concentration in addicted and normal populations. In addition such an in- vivo probe could be invaluable in the evaluation of drug regimens for curbing cocaine addiction and preventing cocaine-induced cardiotoxicity. On the other hand, the same probe radiolabelled with 125I, could be used for the in-vitro characterization of cocaine receptors in mammalian tissues and to fully understand the cellular mechanism of cocaine addiction and cardiotoxicity.